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US FDA•United StatesAL•Approval Letter

Approval Letter Other 211964 (Jan 1, 2021)

Issued January 1, 2021

Issued

January 1, 2021

Application

Other • 211964

Review center

Other

Stage

Final Decision

Letter type

Approval Letter

Response due January 1, 2022Product may be marketed.

Summary

The FDA issued a Complete Response Letter for NDA 211964 for viloxazine hydrochloride extended-release capsules, indicating that the application cannot be approved in its present form due to objectionable conditions at a manufacturing facility, issues with prescribing information, carton and container labeling, and the need to add a Medication Guide statement.

Key points

  • Satisfactorily resolve objectionable conditions noted during the review of records from the manufacturing facility (e.g., through a preapproval inspection or adequate facility responses).
  • Review and revise the proposed prescribing information to conform with PLR Requirements, Pregnancy and Lactation Labeling Final Rule, and other relevant regulations and guidances.
  • Include updated content of labeling in structured product labeling (SPL) format in any resubmission.
  • Revise the carton and container labeling to specify 'Viloxazine……. 150 mg (equivalent to 173 mg of viloxazine hydrochloride)' and refer to the FDA Guidance Naming of Drug Products Containing Salt Drug Substances.
  • Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide' or an appropriate alternative to the carton and container labels per 21 CFR 208.24(d).
  • Resubmit the proposed proprietary name (Qelbree) when responding to the application deficiencies.
  • Resubmit the application or take other actions available under 21 CFR 314.110 within 1 year after the date of this letter.
  • Clearly mark any resubmission with 'RESUBMISSION' in large, bolded type at the beginning of the cover letter, stating it is a complete response to the deficiencies.

Cited reasons

  • Unsatisfactory Manufacturing Facility Conditions
  • Unacceptable Carton and Container Labeling (CMC Perspective)
  • Missing Medication Guide Statement on Labels
  • Proprietary Name Resubmission Required
  • The application for viloxazine hydrochloride extended-release capsules received a Complete Response Letter due to objectionable conditions at the manufacturing facility, unacceptable carton and container labeling, a missing Medication Guide statement, and the need to resubmit the proprietary name.

Recommended actions

  • Satisfactorily resolve objectionable conditions noted during the review of records from the manufacturing facility (e.g., through a preapproval inspection or adequate facility responses).
  • Review and revise the proposed prescribing information to conform with PLR Requirements, Pregnancy and Lactation Labeling Final Rule, and other relevant regulations and guidances.
  • Include updated content of labeling in structured product labeling (SPL) format in any resubmission.
  • Revise the carton and container labeling to specify 'Viloxazine……. 150 mg (equivalent to 173 mg of viloxazine hydrochloride)' and refer to the FDA Guidance Naming of Drug Products Containing Salt Drug Substances.
  • Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide' or an appropriate alternative to the carton and container labels per 21 CFR 208.24(d).
  • Resubmit the proposed proprietary name (Qelbree) when responding to the application deficiencies.
  • Resubmit the application or take other actions available under 21 CFR 314.110 within 1 year after the date of this letter.
  • Clearly mark any resubmission with 'RESUBMISSION' in large, bolded type at the beginning of the cover letter, stating it is a complete response to the deficiencies.

Deficiency summary

The application for viloxazine hydrochloride extended-release capsules received a Complete Response Letter due to objectionable conditions at the manufacturing facility, unacceptable carton and container labeling, a missing Medication Guide statement, and the need to resubmit the proprietary name.

Findings

Unsatisfactory Manufacturing Facility Conditions

Severity: critical

During a review of records requested under FD&C act section 704(a)(4) provided by Supernus (FEI: 3005209462) manufacturing facility, FDA noted objectionable conditions. Satisfactory resolution of these objectionable conditions is required (e.g., preapproval inspection or adequate facility responses addressing these conditions) before this application may be approved.

Recommended response: Address objectionable conditions at the manufacturing facility, which may require a preapproval inspection or adequate facility responses, to enable approval.

Cited: FD&C act section 704(a)(4)

Unacceptable Carton and Container Labeling (CMC Perspective)

Severity: major

The Office of Pharmaceutical Quality (OPQ) finds the label attached to your November 5, 2020, email correspondence not acceptable from a Chemistry, Manufacturing, and Controls perspective. The label needs revision to accurately reflect the drug substance content (e.g., 'Viloxazine……. 150 mg (equivalent to 173 mg of viloxazine hydrochloride)').

Recommended response: Revise carton and container labeling to accurately reflect drug substance content as per FDA guidance on naming drug products containing salt drug substances.

Missing Medication Guide Statement on Labels

Severity: major

Add the following bolded statement or appropriate alternative to the carton and container labels per 21 CFR 208.24(d): 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.'

Recommended response: Add the required Medication Guide statement to carton and container labels as specified in 21 CFR 208.24(d).

Cited: 21 CFR 208.24(d)

Proprietary Name Resubmission Required

Severity: minor

The proposed proprietary name, Qelbree, was found acceptable pending approval of the application. It must be resubmitted when responding to the application deficiencies.

Recommended response: Resubmit the proposed proprietary name 'Qelbree' along with the response to other application deficiencies.

Regulatory context

Submission stage
final decision
Regulatory pathway
NDA 505(b)

Impact

Impact score
0.95
Estimated delay
365 days
Estimated rework cost
$0
Subsequent action
resubmission

Strategic insights

Approval is withheld primarily due to critical manufacturing quality system issues identified during facility review, compounded by several deficiencies in product labeling and administrative requirements, necessitating a comprehensive resubmission.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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